Protective antigen antibody augments hemodynamic support in anthrax lethal toxin shock in canines

Amisha V. Barochia, Xizhong Cui, Junfeng Sun, Yan Li, Steven B. Solomon, Thi Sau Migone, G. Mani Subramanian, Sally D. Bolmer, Peter Q. Eichacker

Research output: Contribution to journalArticle

Abstract

Background. Anthrax-associated shock is closely linked to lethal toxin (LT) release and is highly lethal despite conventional hemodynamic support. We investigated whether protective antigen-directed monoclonal antibody (PA-mAb) treatment further augments titrated hemodynamic support.Methods and Results.Forty sedated, mechanically ventilated, instrumented canines challenged with anthrax LT were assigned to no treatment (controls), hemodynamic support alone (protocol-titrated fluids and norepinephrine), PA-mAb alone (administered at start of LT infusion [0 hours] or 9 or 12 hours later), or both, and observed for 96 hours. Although all 8 controls died, 2 of 8 animals receiving hemodynamic support alone survived (median survival times 65 vs 85 hours, respectively; P=.03). PA-mAb alone at 0 hour improved survival (5 of 5 animals survived), but efficacy decreased progressively with delayed treatment (9 hours, 2 of 3 survived; 12 hours, 0 of 4 survived) (P =. 004 comparing survival across treatment times). However, combined treatment increased survival irrespective of PA-mAb administration time (0 hours, 4 of 5 animals; 9 hours, 3 of 3 animals; and 12 hours, 4 of 5 animals survived) (P =. 95 comparing treatment times). Compared to hemodynamic support alone, when combined over PA-mAb treatment times (0, 9, and 12 hours), combination therapy produced higher survival (P =. 008), central venous pressures, and left ventricular ejection fractions, and lower heart rates, norepinephrine requirements and fluid retention (P ≤. 03).Conclusions.PA-mAb may augment conventional hemodynamic support during anthrax LT-associated shock.

Original languageEnglish (US)
Pages (from-to)818-829
Number of pages12
JournalJournal of Infectious Diseases
Volume205
Issue number5
DOIs
StatePublished - Mar 1 2012

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

Cite this

Barochia, A. V., Cui, X., Sun, J., Li, Y., Solomon, S. B., Migone, T. S., Subramanian, G. M., Bolmer, S. D., & Eichacker, P. Q. (2012). Protective antigen antibody augments hemodynamic support in anthrax lethal toxin shock in canines. Journal of Infectious Diseases, 205(5), 818-829. https://doi.org/10.1093/infdis/jir834